Cartilage is a highly specialized connective tissue with distinct morphological and biochemical characteristics. Histologically, it contains spherical chondrocytes surrounded by extensive extracellular matrix. Chondrocytes produce large amounts of cartilage-specific matrix molecules, including type II collagen, aggrecan, link protein, and hyaluronic acid. Hormones and vitamins affect cartilage expression and maturation by regulating the transcription of cartilage genes. During early development, chondrocytes and myoblasts differentiate from a common population of mesodermal cells that has the potential to form either cartilage or muscle. During differentiation, the activation of muscle-specific genes requires the expression of myogenic factors such as Myf-5 and MyoD1. Since chondrocytes originate from the same mesenchyme that produces myoblasts, one could hypothesize that the differentiation factors of both cell types are similar, and that the mechanisms that activate cartilage-specific genes could be related to those for muscle- specific genes. Our objective is to define the mechanisms for activating chondrocyte-specific genes and to elucidate the molecular basis of cartilage development. Using an animal model, we are also identifying the function of cartilage proteins in vivo. We have initiated a new genome project to identify novel genes important for tooth and craniofacial development. Our goal is to discover and characterize previously unknown genes to help understand how tooth and craniofacial tissues develop and to define the molecular defects underlying anomalies of these tissues or oral cancer. Craniofacial anomalies and cancer of the mouth, neck, and head are of major public concern. A large number of genes are believed to be involved in such anomalies and cancers. As an initial step, we have started to identify and catalogue the genes involved in specific stages of tooth and craniofacial development. The identification of genes that have highly location- and stage-specific expression is important since the gene products are likely to have key roles in the formation of craniofacial tissues. It is also expected that mutations in these genes cause anomalies and cancer. This information will also be useful for generating diagnostic reagents, developing methods for disease and birth defect prevention, and for potential gene therapies.